The general objective of this project is the isolation, biological, and molecular characterization of C-type murine leukemia viruses (MuLVs). Major focus has been on the molecular genetics of the pathogenesis in NFS mice of Moloney (Mol) MuLV-induced lymphoma and Friend (Fr) MuLV-induced erythroleukemia and of lymphomagenesis by a helper-independent MCF virus, NS-6 MCF; and biological and molecular characterization of the LP BM5 viruses involved in induction of mouse AIDS. Studies with Mol and Fr recombinant genomes have established that the major determinant of disease specificity lies within that portion of the viral LTR comprising direct repeat sequences identified with transcriptional enhancer signals. Using recombinants constructed between Fr and Mol within this segment disease specificity was found to be encoded throughout the region (in the 5' and 3' halves of the direct repeat and in an adjacent downstream GC-rich region with enhancer-promoter function). In preparation for molecular genetic studies of NS-6 MCF MuLV the molecularly cloned and sequenced genome has been engineered to permit comparison of LTRs. In efforts to determine which of the components of LP BM5 MuLV mixture, a tissue culture stock known to contain both B-tropic ecotropic and MCF MuLVs, several biologically cloned ecotropic and MCF isolates failed to induce disease, alone or in combination. Virus interference studies and molecular and biological analysis of virus derived from single cell clones of infected cells indicate that disease induction is correlated with a defective genome, 5.0 kb in length, which contains MCF-reactive sequences. Spread of virus is dependent on replication competent virus, the ecotropic MuLV likely being the most efficient helper.